In an attempt to determine the forces operating to control the known genetic variation in enzymes and other proteins in natural populations, already revealed by gel electrophoresis, we will carry out a search for amino acid substitutions that are not charge changes, in Drosophila. Methods will include heat sensitivity of enzymes, urea sensitivity, immunologically detectable changes and polypeptide fingerprinting. We will also search for genetic variation in genes controlling the activity of structural gene loci, by surveying natural populations for genetic variants of timing of enzyme appearance and variations in inducibility of enzymes. The appearance of enzyme activity at different loci will be observed on electrophoretic gels. Finally, we will attempt to observe fitness differences associated with different genotypes by challenging them with specific substrates, by measuring the environmental sensitivity of homozygotes and heterozygotes, and by attempting to measure the fitnesses of different genotypes during successive generations of asexual reproduction in aphids.